Optically active anti-1,2-nitroalkanol compounds are useful as precursors of optically active anti-1,2-aminoalcohol compounds.
Optically active anti-1,2-aminoalcohol compounds are generally used as chiral building blocks having very high utility in organic synthetic chemistry, especially medicinal synthetic chemistry. For example, the optically active anti-1,2-aminoalcohol compounds are contained as basic units in pharmaceutical products such as β-agonist, many naturally-occurring biologically active compounds, and the like. Use of optically active anti-1,2-aminoalcohol compounds as starting materials or reaction reagents makes it possible to efficiently and inexpensively produce compounds that can be used for the synthesis of various pharmaceuticals or naturally-occurring biologically active compounds.
Also, the optically active anti-1,2-nitroalkanol compounds themselves are useful as starting materials of pharmaceutical products.
For example, a compound expressed by the following structural formula (anacetrapib), which is regarded to be promising as an inhibitory drug for CETP (cholesteryl ester transfer protein), can be synthesized from optically active anti-1,2-nitroalkanol compounds (see, for example, NPL 1). Note that, in this proposed technique, a racemate of optically active anti-1,2-nitroalkanol compounds is used to obtain anacetrapib through optical resolution.

One known method for anti-selectively producing the optically active anti-1,2-nitroalkanol compounds through catalytic asymmetric reaction is a method of allowing various aldehyde compounds and nitroalkane compounds to react in the presence of optically active tetraaminophosphonium salts (see, for example, NPL 2).
This method, however, has to be performed at an extremely low temperature of −78° C. and has a problem that it cannot be applied as an industrial production method.
In view of this, the present inventors proposed a method for anti-selectively producing optically active anti-1,2-nitroalkanol compounds through catalytic asymmetric reaction and a catalyst used in this reaction (see PTL 1).
In this proposed technique, nitroaldol reaction using various aldehyde compounds and nitroalkane compounds is performed using as a catalyst a heterogeneous composite metallic complex, in which a ligand of a specific amide compound is coordinated with lanthanoid such as neodymium and an alkali metal such as sodium. Use of it attains synthesis of optically active anti-1,2-nitroalkanol compounds with high anti-selectivity and very high enantiomeric excess. Also, the nitroaldol reaction rapidly proceeds even under cooling at about −40° C.
Further, as a catalyst that is useful in anti-selective catalytic asymmetric nitroaldol reaction and is reusable, the present inventors proposed a catalyst obtained by mixing a specific amide compound, a nitroalkane compound, a neodymium-containing compound, a sodium-containing compound, and a carbon structure (see PTL 2).
However, the neodymium-containing compound [Nd(OiPr)3] and the sodium-containing compound [sodium bis(trimethylsilyl)amide (NaHMDS)], serving as starting materials of the catalyst, specifically used in these proposed techniques of the present inventors, are substances that are instable to the atmosphere and thus are necessary to handle in a glove box. In particular, NdO1/5(OiPr)13/5 and Nd(OiPr)3 are very expensive.
Accordingly, at present, there is a demand to provide a catalyst that can be stably prepared and is inexpensive from the viewpoints of enhancing practical usability of anti-selective catalytic asymmetric nitroaldol reaction.